Coronary heart disease (CHD) accounts for 1 of every 7 deaths in the United States (US), with acute incidences of 1.1M annually. Of these, 40% are ST-elevated myocardial infarction (STEMI), which result from a blood clot. Because ischemic heart muscle dies rapidly, time to reperfusion is critical. By 2030, annual CHD medical costs are projected to rise >$820B, while lost productivity exceeding $275B. Early percutaneous coronary intervention (PCI) is the first-line standard of care in the US. However, because PCI centers primarily target urban populations, PCI has shown limited benefit for STEMI patients living in rural communities, which are subject to longer transportation times and system-wide delays. Consequently, more than 80% of transferred STEMI patients do not receive PCI therapy within the recommended 120min from first medical contact, resulting in higher mortality and greater patient costs. Given that over 60M people live in rural communities that are more than 60 miles from a PCI center, it is estimated that nearly 200k STEMI victims will remain without timely access to PCI each year. While clot-dissolving drugs have proven to be effective, physicians remain concerned with their elevated hemorrhage risk. However, it is generally agreed that the value and reach of PCI centers could be extended to rural populations if a safer fibrinolytic therapy could be more widely employed during transfer to the PCI center. Fundamentally, thrombolytic drugs are limited in their effectiveness due to an inability to rapidly diffuse to a clot. Pulse Therapeutics, Inc.?s (PTI?s) patented technology has overcome this limitation. In preliminary work, PTI?s breakthrough technology has been shown to accelerate unconjugated drugs to a clot by using magnetite particles controlled by a magnet workstation. However, in vivo studies confirm that attachment of the FDA- approved drug tenecteplase (TNK) to PTI?s magnetite particles appears to result in superior efficacy at less than one-tenth the standard TNK dose. These studies predict that combining TNK-loaded particles with a very low systemic TNK dose promises to maximize the recanalization potential of the technology. PTI?s objective is to show dramatic improvements in fibrinolysis for STEMI by using TNK-loaded magnetic particles administered alongside a low TNK systemic dose. The proposed scope of work follows from FDA and MHRA meetings which successfully argued the preclinical safety of the unconjugated magnetic particles and workstation. In Phase I, PTI will conduct in vitro and in vivo studies to assess the efficacy of low TNK systemic doses alongside PTI?s TNK-loaded particles. A prototype kit will be developed which will allow trouble-free loading and administration of the magnetic particles and TNK. Lastly, materials will be assembled for an FDA meeting prior to determining Phase II objectives and aims. The proposed technology has dramatic implications for rural STEMI treatment and will directly address the American Heart Association?s concern that ?Where you live should not determine whether you live.?